Date of Graduation

12-2010

Document Type

Dissertation (PhD)

Program Affiliation

Biomedical Sciences

Degree Name

Doctor of Philosophy (PhD)

Advisor/Committee Chair

Dr. Lei Li

Committee Member

Dr. Andreas Bergmann

Committee Member

Dr. Randy J. Legerski

Committee Member

Dr. Mong-Hong Lee

Committee Member

Dr. Guillermina Lozano

Abstract

RMI1 (BLM-Associated Protein 75 or Blap75) is highly conserved from yeast to human. Previous studies have shown that hRMI1 is required for BLM/TopoIII╬▒/RMI1 complex stability and function. However, in vivo functions of RMI1 remain elusive. To address this question, I generated RMI1 knockout mice by homologous replacement targeting. While RMI1+/- mice showed no obvious phenotype, deletion of both RMI1 alleles leads to early embryonic lethality before implantation. I then generated RMI1/p53 double knockout mice. After ionizing radiation treatment at 4Gy, RMI1/p53 double-heterzygous mice showed shortened tumor latency and aggressive tumor types when comparing with wild type, RMI1+/- and p53+/- control cohorts. My study suggests a dual-functional role of RMI1 in early embryonic development and tumor suppression.

Keywords

RMI1, HR, DSB.

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